BACKGROUND: Predicting the efficacy of anthraquinone-based chemotherapy in breast cancer patients is a challenge. This study will evaluate the value of HER2 and TOP2A as predictors of efficacy in patients with early-stage breast cancer receiving anthraquinone-based adjuvant chemotherapy. METHODS: A meta-analysis of data from 5 randomized adjuvant trials comparing anthraquinone-based chemotherapy regimens with cyclophosphamide, methotrexate, and fluorouracil (CMF) regimens was performed. We assessed the status of HER2 and TOP2A genes by fluorescence in situ hybridization. Tumor samples were submitted to an external laboratory for validation. Some patients received anthraquinone-based chemotherapy and others were treated with CMF, and we compared event-free survival and overall survival in 2 HER2 cohorts (HER2 gene amplified and non-amplified tumors) and 3 TOP2A cohorts (normal, amplified and deletion tumors) by calculating hazard ratios (HRs) for both. Note: Although HER2 gene amplification and combining TOP2A amplification with deletion may have value in predicting the efficacy of anthraquinone chemotherapy, our findings do not support the use of anthracyclines only in patients with tumors with HER2 gene amplification or TOP2A abnormalities.